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71.
Hiroko Uemura Yukio Hara Masayuki Endou Katsumi Mori Haruaki Nakaya 《Naunyn-Schmiedeberg's archives of pharmacology》1995,353(1):73-79
We have recently reported that class III antiarrhythmic drugs inhibit the muscarinic acetylcholine (ACh) receptor-operated K+ current (I
K, ACh) in guinea-pig atrial cells by different molecular mechanisms. The data obtained from the patch-clamp study suggest that d,l-sotalol inhibits I
K, ACh by blocking the muscarinic receptors, whereas MS-551 inhibits the K+ current by blocking the muscarinic receptors and depressing the function of the K+ channel itself and/or the guanine nucleotide-binding protein (G protein). This study was undertaken to determine whether the class III antiarrhythmic drugs d,l-sotalol and MS-551 interact with the muscarinic receptors of cardiac and peripheral tissues. Both drugs inhibited concentration dependently the specific [3H]N-methylscopolamine ([3H]-NMS) binding to membrane preparations obtained from guinea-pig atria and submandibular glands. The competition curves of these drugs for [3H]-NMS binding to glandular membranes were monophasic, suggesting competition with [3H]-NMS at a single site. Although the competition curve of d,l-sotalol for [3H]-NMS binding to atrial membranes was monophasic, that of MS-551 was biphasic and showed high- and low-affinity states of binding. d,l-Sotalol showed slightly, but significantly, higher affinity for cardiac-type muscarinic receptors (M2) than for glandular-type muscarinic receptors (M3). The inhibition constant (K
i) for MS-551 in glandular membranes was also slightly greater than the high-affinity K
i value for the drug in atrial membranes. In guinea-pig left atria and ilea, d,l-sotalol shifted the concentration-response curves for the negative inotropic effect and the contracting effect of carbachol in a parallel manner. The slopes of Schild plot were not significantly different from unity, suggesting competitive antagonism, and the pA2 for d,l-sotalol in left atria was slightly greater than that in ilea. MS-551 also shifted the concentration response curve for the negative inotropic effect of carbachol in atrial preparations to a greater extent than that for the contracting effect in ileal preparations, although MS-551 failed to show a pure competitive antagonism. These results suggest that both d,l-sotalol and MS-551 interact with cardiac M2 and peripheral M3 receptors, and that at high concentrations they exert anticholinergic activity in cardiac and peripheral tissues. 相似文献
72.
Total Esophagectomy versus Proximal Esophagectomy for Esophageal Cancer at the Cervicothoracic Junction 总被引:1,自引:0,他引:1
Fujita H Kakegawa T Yamana H Sueyoshi S Hikita S Mine T Tanaka Y Ishikawa H Shirouzu K Mori K Inoue Y Tanabe HY Kiyokawa K Tai Y Inutsuka H 《World journal of surgery》1999,23(5):486-491
To investigate the adequate extent of esophagectomy and lymphadenectomy for an esophageal cancer localized at the cervicothoracic
junction, the mortality and morbidity rates, survival rates, and patterns of recurrence were retrospectively analyzed in two
groups—14 patients who underwent total esophagectomy with or without laryngectomy and 15 patients who underwent proximal esophagectomy
with or without laryngectomy—at Kurume University Hospital from 1981 to 1996. Proximal esophagectomy with or without laryngectomy
resulted in a lower hospital mortality rate and better overall survival for patients who underwent curative esophagectomy
compared with total esophagectomy with or without laryngectomy. Multivariate analysis indicated that the extent of esophagectomy
(total esophagectomy versus proximal esophagectomy) was not a prognostic factor. The incidence of recurrence was not different
between the two groups. Lymph node metastasis or recurrence from such esophageal cancers was localized to the neck and upper
mediastinum. For an esophageal cancer localized at the cervicothoracic junction, therefore, proximal esophagectomy with or
without laryngectomy and with cervical and upper mediastinal lymphadenectomy could be better indicated for preselected patients. 相似文献
73.
Impaired glucose tolerance, diabetes mellitus, and gallstone disease: An extended study of male self-defense officials in Japan 总被引:2,自引:0,他引:2
Shizuka Sasazuki Suminori Kono Isao Todoroki Satoshi Honjo Yutaka Sakurai Kazuo Wakabayashi Masato Nishiwaki Hiroaki Hamada Hiroshi Nishikawa Hiroko Koga Shinsaku Ogawa Katsuya Nakagawa 《European journal of epidemiology》1999,15(3):245-251
Few studies have investigated the relation between glucose tolerance status and ultrasonographically determined gallstone disease. Using a 75-g oral glucose tolerance test, we examined the association of impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) with gallstone disease in Japanese men. Subjects were men aged 48 to 59 of the Japan Self-Defense Forces who received a preretirement health examination between October 1986 to December 1994. After exclusion of 12 men under insulin treatment in the consecutive series of 7637 men, 174 were found to have gallstones; 103 were at the state of postcholecystectomy, and 6899 had normal gallbladder. IGT and NIDDM were associated with a modestly increased risk of gallstone disease; adjusted odds ratios were 1.3 (95% confidence interval [CI]: 0.9–1.8) for IGT and 1.3 (95% CI: 0.8–2.0) for NIDDM after adjustment for hospital, rank, smoking, alcohol use, and body mass index. Adjusted odds ratio for IGT and NIDDM combined was 1.3 (95% CI: 1.0–1.7, p=0.08). When prevalent gallstones and postcholecystectomy were considered separately, NIDDM showed a significant, positive association with postcholecystectomy, but not with prevalent gallstones. The findings add to evidence that glucose intolerance is associated with a modest increase in the risk of gallstone disease. 相似文献
74.
Machiko Matsumoto Mitsuhiro Yoshioka Hiroko Togashi Toshiya Ikeda Hideya Saito 《Naunyn-Schmiedeberg's archives of pharmacology》1996,353(6):621-629
The functional regulation by dopamine (DA) receptors of serotonin (5-HT) release from the rat hippocampus was investigated by use of in vivo microdialysis. Dialysate 5-HT levels were reduced by co-perfusion of 10 M tetrodotoxin (TTX) and were elicited by K+ (60 and 120 mM) stimulation in a concentration-dependent manner. Local perfusion (10 M) and peripheral administration (20 mg/kg, i.p.) of fluoxetine produced increases in 5-HT levels. These results indicate that the spontaneous 5-HT levels in the rat hippocampus can be used as indices of neuronal origin from the serotonergic nerve terminals. The nonselective dopamine (DA) receptor agonist apomorphine (1, 10 and 100 M), when perfused through the probe over a period of 40 min, increased 5-HT release in a concentration-dependent manner. Apomorphine-induced (100 M) increases in 5-HT release was abolished by pretreatment with the selective D2 receptor antagonist, S(–)-sulphide (1 and 10 M), but not prevented by pretreatment with the selective D1 receptor antagonist, R(+)-SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) (1 M). S(–)-Sulpiride and R(+)-SCH-23390 by themselves did not alter the spontaneous 5-HT levels. The 5-HT release was elevated by perfusion of the selective DA reuptake inhibitor GBR 12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine)(1, 10 and 100 M), indicating the possibility of not only exogenous but also endogenous DA-mediated facilitatory effects on 5-HT release in vivo. The 5-HT release was also elevated by perfused (±)-PPHT ((±)-2-(N-phenylethyl-N-propyl)-amino-5-hydroxytetralin)(1, 10 and 100 M), the selective D2 receptor agonist, in a concentration-dependent manner. On the other hand, (±)-PPHT (100 M) failed to increase 5-HT release in catecholamine (CA)-lesioned rats pretreated with 6-hydroxydopamine (6-OHDA)(200 g/rat, i.c.v.). The (±)-PPHT-induced (100 M) increase in 5-HT release was prevented not only by pretreatment with 10 M S(–)-sulphide but also by pretreatment with the 2-adrenoceptor antagonist idazoxan (10 M). These findings suggest that the functional regulation of 5-HT release via D2 receptors exists in the rat hippocampus. Furthermore our results indicate that the facilitatory effect of 5-HT release via D2 receptors may be mediated indirectly by noradrenergic neurons, but not mediated directly through D2 receptors located on serotonergic nerve terminals. 相似文献
75.
To investigate cholecalciferol (vitamin D) metabolism disorders in hepatic osteodystrophy (HOD) and the effects of vitamin D, its metabolites, and calcium (Ca) on HOD, an experimental HOD model in rats was developed using carbon tetrachloride. In the serum level of 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol, and 24R,25-dihydroxycholecalciferol, there were no significant differences between normal and control cirrhotic rats. Vitamin D supplementation significantly inhibited the atrophy of intestinal villi, reduction of bone calcium content, elevation of bone resorption, reduction of osteoid volume, and reduction of bone volume. Ca supplementation significantly increased the serum free Ca index and inhibited the elevation of bone resorption, the reduction of bone ash and Ca content, and the reduction of bone volume. This experimental study demonstrates that: (1) no marked vitamin D hydroxylation disorder was found in HOD; (2) vitamin D supplementation was effective in inhibiting HOD; and (3) sufficient Ca supplementation was also effective in inhibiting HOD.A portion of this work was presented at the 13th Annual Meeting of the Japanese Society for Bone and Mineral Research, July 1995, Fukuoka, Japan. 相似文献
76.
Kazuo Nomiyama Mamoru Yotoriyama Hiroko Nomiyama 《Archives of environmental contamination and toxicology》1983,12(2):143-146
Urinary
2-microglobulin (MG) was determined in 99 elderly people above 50 years of age from an area with no known cadmium pollution. With advancing age, the urinary MG increased as well as the urinary protein, urinary retinol-binding protein (RBP), and plasma urea nitrogen. Nevertheless, age effects were not observed in renal functions such as creatinine clearance or tubular reabsorption of phosphorus. Analysis of the relationship between urinary MG and parameters of the renal functions suggested 2-step increases in urinary MG: a slight increase between 160 and 1600g/L and a remarkable increase above 1600g/L. The latter strong increase in urinary MG was closely related with depressed tubular reabsorption of MG, but was independent of tubular reabsorption of phosphorus. The screening level of urinary MG for renal tubular dysfunction is suggested at 1600g/L. 相似文献
77.
Tetsuya Yamada Gaku Ichihara Hailan Wang Xiaozhong Yu Kei-ichiro Maeda Hiroko Tsukamura Michihiro Kamijima Tamie Nakajima Yasuhiro Takeuchi 《Toxicological sciences》2003,71(1):96-103
Although 1-bromopropane has been used in chemical and electronic industries as an alternative to ozone layer-depleting solvents, its toxicity on female reproductive organs has not been fully elucidated. The aim of this experiment was to determine the effect of 1-bromopropane on female reproductive function in rats. Forty female Wistar rats were divided into four equal groups. Each group was exposed daily to 0, 200, 400, or 800 ppm of 1-bromopropane for eight h a day. After exposure for 7 weeks, all rats in the 800-ppm group became seriously ill and were sacrificed during the 8th week. The other dose groups were exposed for 12 weeks. In the 800-ppm group, but not in the other two exposed groups, body weight was significantly less than the control at each time point from 2 to 7 weeks after the beginning of exposure. Tests of vaginal smears showed a significant increase in the number of irregular estrous cycles with extended diestrus in the 400- and 800-ppm groups. Histopathological examination of the ovary showed a significant dose-dependent reduction of the number of normal antral follicles and a decrease in the number of normal growing follicles in the 400-ppm group. No significant change was found in plasma concentrations of LH or FSH in any group when compared with the control. Our results indicate that 1-bromopropane can induce a dose-dependent ovarian dysfunction in nonpregnant female rats associated with disruption in follicular growth process. 相似文献
78.
79.
Ken-ichi Ueno Hiroko Togashi Mitsuhiro Yoshioka 《Nihon shinkei seishin yakurigaku zasshi》2003,23(1):47-55
The present study was undertaken to evaluate juvenile stroke-prone spontaneously hypertensive rats (SHRSP) as an animal model of attention-deficit/hyperactivity disorder (AD/HD). Juvenile SHRSP showed significant increases in horizontal ambulatory activity and vertical rearing activity in the open field as compared with genetic control Wistar-Kyoto rats (WKY). Anxiety-related behavior assessed by elevated plus-maze as an index of impulsivity, the entries into open arms and the spent time in the open arms of SHRSP were significantly higher than those of WKY. Spontaneous alternation behavior requiring attention and working memory in the Y-maze was significantly impaired in male, but not female, SHRSP when compared with sex-matched WKY. Hippocampal long-term potentiation formation, a cellular model of learning and memory, was not impaired in SHRSP. Methylphenidate, a first choice psychostimulant for AD/HD, significantly alleviated the hyperactivity in SHRSP. However, intense impulsivity of SHRSP was not improved by methylphenidate. Methylphenidate dose-dependently and significantly ameliorated the impaired spontaneous alteration behavior in male SHRSP. These results suggest that juvenile male SHRSP manifest problematic behavior resembling ADHD, namely inattention, hyperactivity and impulsivity. Methylphenidate alleviates the behavioral symptoms of hyperactivity and inattention. Thus, juvenile male SHRSP might be a useful behavioral animal model of AD/HD, from behavioral and pharmacological perspectives. 相似文献
80.
Increased Sensitivity to Long-term 5-Fluorouracil Exposure of Human Colon Cancer HT-29 Cells Resistant to Short-term Exposure 总被引:3,自引:1,他引:3
A 5-fluorouracil (5-FU)-resistant subline of human colon cancer HT-29 cells was developed by repeated 1-h exposure in vitro to 5-FU. This subline (HT-29/5-FU/S) had 8-fold resistance to 5-FU in a 1-h exposure assay. However, it had rather increased sensitivity to 5-FU when assayed after a continuous 96-h exposure to it. Significantly less 5-fluorouridine-5'-triphosphate was produced in the resistant cells, leading to a lower level of 5-FU incorporation into the cellular RNA. The reduced activity of orotate phosphoribosyltransferase might explain these results. In contrast, the HT-29/5-FU/S cells were more sensitive to the inhibition of in situ thymidylate synthase (TS) by 5-FU than were the parent cells. The lower in situ TS activity may have made HT-29/5-FU/S cells more sensitive to TS inhibition by 5-FU as compared with the parent cells. The fact that HT-29/5-FU/S was more resistant to short-term 5-FU exposure but more sensitive to long-term exposure than the parent line confirmed the existence of different modes of action of 5-FU, depending on the exposure time. 相似文献